Safety Evaluation of COVID-19 Vaccine in Patients With IgA Nephropathy or IgA Vasculitis Nephritis

Abstract

IgA nephropathy (IgAN) is the most commonly reported glomerulonephritis associated with COVID-19 vaccine.1Stevens K.I. Frangou E. Shin J.I. et al.Perspective on COVID-19 vaccination in patients with immune-mediated kidney diseases: consensus statements from ERA-IWG and EUVAS.Nephrol Dial Transplant. Published online March 4, 2022; https://doi.org/10.1093/ndt/gfac052Crossref PubMed Scopus (2) Google Scholar,2Klomjit N. Alexander M.P. Fervenza F.C. et al.COVID-19 vaccination and glomerulonephritis.Kidney Int Rep. 2021; 6: 2969-2978https://doi.org/10.1016/j.ekir.2021.09.008Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar As an immunostimulant, safety is the principal concern of patients with IgAN. Lim et al.3Lim C.C. Choo J. Tan C.S. COVID-19 vaccination in immunoglobulin A nephropathy.Am J Kidney Dis. 2021; 78: 617https://doi.org/10.1053/j.ajkd.2021.07.001Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar reported that no patient experienced gross hematuria and serum creatinine level of a few patients rose slightly. However, the vaccine type was restricted to mRNA vaccine and the sample size was small. Thus, the safety of COVID-19 vaccine in the population of IgAN still needs to be fully explored. We retrospectively investigated 965 patients with IgAN or IgA vasculitis nephritis, and 46% (443 of 965) of the patients received at least 1-dose vaccination (Supplementary Figure S1). Of these, 76 patients vaccinated before kidney biopsy were excluded. Finally, 367 vaccinated patients were included for primary safety evaluation. Most (351 of 367, 96%) patients were injected an inactivated vaccine (CoronaVac or BBIBP-CorV). There were 2 (0.5%, 95% CI, 0.07%–2.0%) flare-up events reported by patients and adjudicated. After 2 weeks from receiving the first dose, 1 patient experienced gross hematuria episode. Another developed nephrotic syndrome, 3 months after the second dose. The 2 patients started or escalated their immunosuppressive therapy after exacerbation. Further analysis revealed that 3 patients exhibited >30% estimated glomerular filtration rate decrease and 3 patients progressed to nephrotic proteinuria within 3 months. Overall, 6 (1.6% [0.6%–3.5%]) composite kidney adverse events were adjudicated (Table 1). The subsequent change of these patients was displayed in Supplementary Figure S2.Table 1The characteristics of the patients developing kidney adverse eventsPatientAge/SexVaccineBaselinePostvaccinationeGFR, ml/min per 1.73 m2Proteinuria, g/dIS132/FCoronaVac1080.35NoGross hematuria 2 wk later; received immunosuppressive therapy.240/FCoronaVac90.11.04No>30% eGFR decline within 3 mo.335/FCoronaVac63.80.09Yes>30% eGFR decline; progressed to nephrotic syndrome within 3 mo;adjusted immunosuppressive regime.436/MCoronaVac66.30.73Yes>30% eGFR decline within 2 mo.536/MCoronaVac61.22.28NoProgressed to nephrotic proteinuria within 3 mo.637/FBBIBP-CorV25.21.14NoProgressed to nephrotic proteinuria within 2 mo.eGFR, estimated glomerular filtration rate; F, female; IS, immunosuppressants; M, male. Open table in a new tab eGFR, estimated glomerular filtration rate; F, female; IS, immunosuppressants; M, male. Furthermore, 202 patients received blood and urine tests within 3 months before and after vaccination were available for further statistical analysis. There was no significant difference between the baseline and postvaccination proteinuria (0.59 [interquartile range, 0.30–0.98] vs. 0.54 [0.33–0.92] g/d; P = 0.52) and hematuria (25.1 [8.9–72.2] vs. 25.4 [9–59.2]/μl; P = 0.47). Estimated glomerular filtration had a mild but statistically significant difference (68.39 [23.18] vs. 67.33 [23.53] ml/min per 1.73 m2; P = 0.03) from prevaccination to postvaccination (Table 2).Table 2Baseline and postvaccination characteristics of included patientsCharacteristicsBaseline (n = 202)Postvaccination (n = 202)P valueAge, yr, mean (SD)41.5 (11.3)—— Sex Male107 (53.0)—— Female95 (47.0)——Disease IgA nephropathy197 (97.5)—— IgA vasculitis nephritis5 (2.5)——Vaccine Inactivated vaccine192 (95.0)—— Recombinant subunit vaccine10 (5.0)——eGFR, ml/min per 1.73 m2, mean (SD)68.39 (23.18)67.33 (23.53)0.03at test.Hematuria, /μl, median (IQR)25.1 (8.9–72.2)25.4 (9–59.2)0.52bWilcoxon signed-rank test.Proteinuria, g/d, median (IQR)0.59 (0.30–0.98)0.54 (0.33–0.92)0.47bWilcoxon signed-rank test.IS use during vaccination31 (15.3)——eGFR, estimated glomerular filtration rate; IQR, interquartile range; IS, immunosuppressants.Values are presented as n (%), unless otherwise indicated.a t test.b Wilcoxon signed-rank test. Open table in a new tab eGFR, estimated glomerular filtration rate; IQR, interquartile range; IS, immunosuppressants. Values are presented as n (%), unless otherwise indicated. Overall, the absolute incidence of adverse events was low, and COVID-19 vaccine was well tolerated in patients with IgAN, especially to those having relatively stable disease. Although glomerular filtration rate decline was observed in a few patients, the change was temporary. But close monitoring of the kidney function after vaccination should be offered to intervene as early as possible. Download .pdf (1.68 MB) Help with pdf files Supplementary File (PDF) Figure S1. Research flowchart of the study. IgAN, IgA nephropathy; IgAVN, IgA vasculitis nephritis. Figure S2. The eGFR and proteinuria changes of the 6 patients developing adverse event during follow up. eGFR, estimated glomerular filtration rate.